Application Of Sp~2C-H Alkylation In The Synthesis Of Coumarin And Naphthoquinone Derivatives

C-H functionalization has always been the most economical,efficient,and convenient way to construct C-C bonds.Selective alkylation modification of drug molecules can not only improve their liposolubility,but also enhance the stability.It is one of the most important research directions of C-C bond construction in synthetic chemistry.Nowadays,the transition metal catalysis induced by the directing group has gradually been difficult to meet the society's demand for green,economic,and efficient reactions.The development of inexpensive and non-toxic metal-catalyzed alkylation reactions is one of the current research hotspots for chemists.In addition,with the vigorous development of visible-light redox catalysis,visible-light-catalyzed radical coupling reaction has become a novel protocol to building C-C bonds.This thesis focuses on two parts of work involving the synthesis of coumarin derivatives using cheap-metal catalysis and visible-light-induced regioselective alkylation of 1,4-naphthoquinones.The specific contents include the following three aspects:The first chapter summarizes the overview of sp²C-H bond alkylation in recent years,highlighting the research progress of radical sp²C-H bond alkylation,and related research results are discussed in terms of catalytic system,reaction mechanism,and substrate practicality.The Chapter 2 introduces the selective alkylation of coumarin and chromone catalyzed by a cheap metal iron salt.Using Fe?OTf?₃as the catalyst and diacyl peroxide as the alkylating agent,a simple and efficient method for constructing C_sp2-C_sp3 bond was developed.Through the screening of the reaction system including catalyst,solvent,and reaction temperature,the optimal reaction conditions were obtained,and 25 examples of?-linear alkyl substituted coumarins compounds and 8examples of?-linear alkyl substituted chromones were synthesized with moderate to good yields?40%?83%?.The radical decarboxylation coupling mechanism was verified by radical trapping experiments.The salient features of this method include the use of inexpensive non-toxic metal catalysts,no need to add any ligands and additives,high regioselectivity,easily obtained starting materials,and simple reaction operation.In chapter 3,a tandem cyclization reaction of two components catalyzed by visible light without metal photosensitizer was introduced,and 2-amino-1,4-naphthoquinone derivatives substituted by C-3 alkyl lactam were synthesized efficiently.The reaction used blue LED lamp as the light source,N-allyl-2-bromine-2,2-difluoroacetylamine as the cyclic substrates,and 9 examples of C-3 alkyl lactam substituted 2-amino-1,4-naphthoquinone derivatives were synthesized in medium to good yields?48%to 78%?through intramolecular cyclization and intermolecular coupling reaction with 2-amino-1,4-naphthoquinone catalyzed by the cheap photosensitizer Fluorescein and organic amine PMDETA.This method provides a new way to synthesize 1,4-naphthoquinone derivatives,which has the advantages of cheap and green catalyst,mild reaction conditions,and wide range of substrate applications.